The development of tools for the early diagnosis of pancreatic adenocarcinoma is an urgent need in order to increase treatment success rate and reduce patient mortality. Here, we present a modular nanosystem platform integrating soft nanoparticles with a targeting peptide and an active imaging agent for diagnostics. Biocompatible single-chain polymer nanoparticles (SCPNs) based on poly(methacrylic acid) were prepared and functionalized with the somatostatin analogue PTR86 as the targeting moiety, since somatostatin receptors are overexpressed in pancreatic cancer. The gamma emitter Ga was incorporated by chelation and allowed in vivo investigation of the pharmacokinetic properties of the nanoparticles using single photon emission computerized tomography (SPECT). The resulting engineered nanosystem was tested in a xenograph mouse model of human pancreatic adenocarcinoma. Imaging results demonstrate that accumulation of targeted SCPNs in the tumor is higher than that observed for nontargeted nanoparticles due to improved retention in this tissue.

Synthesis and Functionalization of Dextran-Based Single-Chain Nanoparticles in Aqueous Media IK4-CIDETEC, Pº Miramón 196, 20014, Donostia-San Sebastián, Spain. b. Radiochemistry and Nuclear Imaging Group, CIC biomaGUNE, Pº Miramón 182, 20014, Donostia-San Sebastián, Spain. Water-dispersible dextran-based single-chain polymer nanoparticles (SCPNs) were prepared in aqueous media and mild conditions. Radiolabeling of the resulting biocompatible materials allowed the study of lung deposition of aqueous aerosols after intratracheal nebulization by means of single-photon emission computed tomography (SPECT), demostrating their potential use as imaging contrast agents.Advances in engineering polymer chains at the molecular level 1 have pushed the development of synthetic strategies for the controlled compaction of single polymer coils into unimolecular soft nano-objects, named single-chain polymer nanoparticles (SCPNs).2-4 SCPNs based on synthetic polymers benefit from the possibility of a controlled construction of the precursors in order to prepare tuned SCPNs with desired size and functionality.3 Additionally, a wide variety of biocompatible, non-toxic and ready-to-use natural polymers are available. Consequently, SCPNs have gained interest as potential mimetics of biomacromolecules such as proteins 5,6 and for application in different fields including nanomedicine.7-9 Among natural polymers, polysaccharides can be envisaged as natural analogues of polyethylene glycol (PEG). For example, dextrans have been used in several biomedical applications due to aqueous solubility, biocompatibility, biodegradability, wide availability, ease of modification and non-fouling properties.10,11 However, in vivo application of SCPNs can be limited due to their small size. Rapid blood clearance is expected after intravenous administration of particles below 5 nm size. 12 In the last years, non-invasive lung administration route has been broadly studied, 13 and SCPNs could be beneficial due to their small size.14 Synthetic routes to SCPNs are mainly based on intrachain homo-and hetero-coupling or cross-linking-induced collapseof pre-functionalized polymers through covalent, dynamic covalent, and non-covalent bonding. 15,16 Most of the covalent strategies are performed in organic solvents and require highly diluted polymer solutions (usually <1 mg/mL), high temperatures and/or the presence of metal catalysts. The preparation of SCPNs through "continuous addition" avoids ultra-dilution conditions, which is beneficial for multigram scale preparations. 17 Recently, it has been described that the presence of oligo(ethylene glycol) brushes as side-chains allows to achieve SCPNs at high polymer concentrations (100 mg/mL). 18 However, the development of general procedures to obtain functionalizable SCPNs in aqueous media, mild conditions and scalable conditions is still a challenging issue.Our group reported a strategy to generate structurally defined and water-dispersible poly(methacrylic acid)-based SCPNs.19 In pursuit of novel types of...

Interstitial cystitis (IC) is a progressive bladder disease characterized by increased urothelial permeability, inflammation of the bladder with abdominal pain. While there is no consensus on the etiology of the disease, it was believed that restoring the barrier between urinary solutes and (GAG) urothelium would interrupt the progression of this disease. Currently, several treatment options include intravesical delivery of hyaluronic acid (HA) and/or chondroitin sulfate solutions, through a catheter to restore the urothelial barrier, but have shown limited success in preclinical, clinical trials. Herein we report for the first time successful engineering and characterization of biphasic system developed by combining cross‐linked hyaluronic acid and naïve HA solution to decrease inflammation and permeability in an in vitro model of interstitial cystitis. The cross‐linking of HA was performed by 4‐arm‐polyethyeleneamine chemistry. The HA formulations were tested for their viscoelastic properties and the effects on cell metabolism, inflammatory markers, and permeability. Our study demonstrates the therapeutic effects of different ratios of the biphasic system and reports their ability to increase the barrier effect by decreasing the permeability and alteration of cell metabolism with respect to relative controls. Restoring the barrier by using biphasic system of HA therapy may be a promising approach to IC.